The use of parenteral fluids (e.g., involving an administrative pathway other than one which involves the gastrointestinal tract) in health care has grown rapidly over the past several years. For example, since some individuals are unable to receive medication by enteral means, and some medications are less efficient when taken enterally, the use of parenterally administered drugs is preferred.
Parenteral administration typically includes intravascular, intramuscular, or subcutaneous routes, but drugs may be applied to the skin or injected intradermally, for local effect or to be absorbed percutaneously; they may be inhaled for direct action on the bronchial tree or to be absorbed into blood at the alveoli; they may be injected into or near the spinal canal; or they may be introduced intravaginally. Different routes may be used for different reasons. For example, intravascular administration routes may be used to administer large quantities of fluid over a long period of time by means of a continuous infusion apparatus. Also, intravascular administration is usually the safest way to administer a drug that has a narrow margin of safety between therapeutic and toxic blood levels or is easily contaminated. Large amounts of solution may also be introduced intramuscularly, and there is usually less pain and local irritation than is encountered by the subcutaneous route. However, subcutaneous administration may also be advantageous, e.g., when the drug is intended to have local, rather than systematic, effect. With respect to inhalation of drugs, some drugs, particularly volatile anesthetics, may function best when inhaled as aerosols.
Unfortunately, while the parenteral administration of fluids such as medicaments may be advantageous, it is not without drawbacks. For example, infection during the administration process is a potentially major complication, even though medicaments may be produced according to strict regulations, e.g., strict aseptic protocols, and the preparation may be highly uniform. Microbiologic contamination of parenterally administered substances may occur during their preparation, during administration, or via manipulation of a part of the administration set, e.g., a catheter, thus leading to infection. The threat of infection is of particular concern when administering parenteral fluids to debilitated patients with compromised immune systems, since their resistance to infection may be low.
The problem may be magnified since parenterally administered medicaments, particularly those containing lipids, may provide a medium for the rapid growth of potentially pathogenic microorganisms, including bacteria and fungi. For example, fungal organisms, such as Candida albicans, and bacterial organisms such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus spp. may thrive in a variety of medicament administration systems, therefore posing a threat of infection.
Additionally, pyrogenic substances, for example, pyrogens of bacterial origin, e.g., endotoxins such as lipopolysaccharide complexes in the parenteral fluid, can induce fever. Moreover, failure to maintain aseptic protocols may lead to infection caused by pathogenic contaminants.
There are additional drawbacks associated with parenterally administered fluids. Part of the problem relates to the composition and characteristics of the parenteral fluid. A typical parenterally administered medicament may include an oil-in-water emulsion wherein lipids are a primary component of the emulsion. The lipid emulsion is typically stabilized by an emulsifying agent such as a phospholipid, which gives the emulsion droplets a negative surface charge, e.g., a zeta potential of about -40 mV. The negatively charged emulsion droplets repel each other, which contributes to the stability of the system by maintaining the homogenous dispersion of the lipid particles within the internal phase of the emulsion. If homogenous dispersion is not maintained, the emulsion may destabilize, and the particles may aggregate in larger numbers, and coalesce to form larger particles. This may pose a great threat to the patient if this parenteral fluid is administered, since particles greater than about 5 micrometers in size may block small pulmonary vessels, causing a potentially dangerous fat embolus.
Additionally, parenterally administered fluids, particularly those containing a lipid emulsion component, may be opaque, making proper inspection for undesirable matter, e.g., large coalesced particles resulting from the instability of the lipid emulsion, particulates, drug-drug coprecipitates, microorganisms, and/or air, impossible. More importantly, visual inspection for undesirable particulate matter is of limited value, since the destabilization of the emulsion would not be visually apparent until the coalesced lipid particles are about 40 to 50 micrometers in size, which is far greater than the minimum size particle (i.e., about 5 micrometers) that might pose a threat to a patient.
Attempts to minimize microbiological contamination and growth in parenteral administration systems have focused on the use of strict aseptic techniques and single-use products, rather than on the use of microbiological filters. For example, microbiological filters are specifically contra-indicated by some manufacturers of parenteral medicaments. It is believed that the filter may cause a breakdown of the emulsion, and the filter may exhibit limited flow capacity, may plug easily and/or may bind or restrict the flow of the medicament. Moreover, the pore rating of a microbiological filter may be expected to block desirable material, such as lipid particles in an emulsion, since those particles may have a diameter of about 0.5 micrometers or less.
All of these situations may present great risk to the patient. If the emulsion breaks down, or the medicament is blocked, the filter and administrative process may be rendered ineffective. If the flow rate is adversely affected, the medical personnel may need to constantly monitor the flow with the fear that the filter may plug and have to be replaced during a medical procedure, which exposes the patient to additional risks, e.g., insufficient medication and/or septic contamination.
Furthermore, the decrease in flow of parenterally administered medicaments which pass through a microbiological filter may pose an additional drawback--excessive pressure build up. Excessive pressure build up may be a serious problem with parenteral systems since the liquid medicament may be administered using a pump designed to operate at relatively low pressures, e.g., less than 25 psi, typically less than 15 psi, and, in some applications, at less than 10 psi. Because these pumps are not engineered to operate at higher pressures, the parenteral fluid administration system typically includes an occlusion alarm which shuts down the pump at a relatively low pressure. This places an additional constraint on the use of anti-microbiological filters having a pore rating below about 1.2 micrometers, since these filters may exhibit pressure build up, flow restriction, and plugging that leads to pump shut down.
Thus, the administration of parenteral fluids, particularly parenteral medicaments, typically reflects an unsatisfying compromise. On the one hand, strict aseptic techniques and single use products may decrease contamination and growth without adversely affecting the emulsion or the flow rate, but these techniques still fail to provide for the administration of a bacteria-depleted infusate to the patient. On the other hand, pore ratings sufficient to remove microorganisms are typically too small to be used effectively with parenteral fluids and with some medicaments administered parenterally. This is an especially unsatisfying compromise since bacteria and/or fungi are likely to grow in media used for parenteral medicaments, especially those medicaments containing a lipid component.
There is, therefore, a need for a filter device for a parenterally administered medicament having an enhanced capability for filtration of undesirable matter from a parenteral medicament fluid, especially to preclude microorganisms and fine particles from entering the infusate while passing the larger, desirable, parenteral medicament fluid components therethrough. In particular, there is an urgent need for a filter for processing a parenteral medicament fluid including a lipid emulsion and a medicament to remove bacteria from an infusate.